Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Cell. 2020 Aug 20;182(4):828-842.e16. doi: 10.1016/j.cell.2020.06.025. Epub 2020 Jun 24.

Abstract

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

Keywords: COVID-19; ELISA; Fab; IgG; MERS-CoV; SARS-CoV; SARS-CoV-2; convalescent plasma; coronavirus; electron microscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / isolation & purification
  • Antibodies, Viral / immunology
  • Antibodies, Viral / isolation & purification
  • Betacoronavirus / chemistry*
  • Betacoronavirus / immunology
  • COVID-19
  • Coronavirus Infections / blood
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / therapy
  • Cross Reactions
  • Cryoelectron Microscopy
  • Epitope Mapping
  • Epitopes
  • Humans
  • Immunization, Passive
  • Immunoglobulin Fab Fragments / blood
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / isolation & purification
  • Immunoglobulin Fab Fragments / ultrastructure
  • Immunoglobulin G / blood
  • Immunoglobulin G / chemistry*
  • Immunoglobulin G / isolation & purification
  • Immunoglobulin G / ultrastructure
  • Middle East Respiratory Syndrome Coronavirus / chemistry
  • Middle East Respiratory Syndrome Coronavirus / immunology
  • Models, Molecular
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / immunology*
  • SARS Virus / chemistry
  • SARS Virus / immunology
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • COVID-19 serotherapy